Inhibitors of STAT3 and uses thereof

US8841257B2 · kind B2 · utility

Assignee

• The Board of Regents of the University of Texas System · US

Inventors

• John S. McMurray · Houston, US
• Pijus Kumar MANDAL · Rua Engenheiro Marcondes Ferraz, US
• Warren S. Liao · Houston, US
• Fredika Robertson · Houston, US
• Xiaomin Chen · Houston, US
• Ramesh Rajaopal · Saginaw, US
• Zhiyong Ren · Houston, US

Key dates

• Filing date: Apr 9, 2010
• Grant date: Sep 23, 2014
• Expiry date: Oct 8, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/6561
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Compounds which inhibit the activity of signal transducer and activator of transcription 3 (STAT3) are provided together with methods of making and using the same. The compounds are designed to bind to the SH2 domain of STAT3, preventing STAT3 from binding to receptors for interleukin-6 family cytokines, growth factors such as the platelet-derived growth factor, the epidermal growth factor, vascular endothelial growth factor, and other signaling molecules such as leptin. Blocking these interactions prevents STAT3 from being phosphorylated on Tyr705, which is required for the dimerization of STAT3, translocation to the nucleus, binding to STAT3 response elements on promotors, and transcription of genes. In addition to these activities, binding to the SH2 domain of STAT3 breaks up pre-formed dimmers, thereby preventing the transcriptional activity of the inhibitor.